To develop an effective ocular drug delivery carrier, we prepared two different charged gelatin nanoparticles (GPs) and evaluated particle size, surface charge, and morphology. The in vitro biocompatibility of GPs was assessed using human corneal epithelium (HCE) cells and in vivo safety by administering them as eye drops to New Zealand rabbits. The GPs prepared using type A gelatin were positively charged (GP(+), +33 mV; size, 180.6 ± 45.7 nm). Water‐soluble tetrazolium salt (WST)‐1 assay showed that both GPs were nontoxic to HCE cells. The fluorescence intensity of HCE cells cultured with cationic GPs conjugated with a fluorescent dye was higher than that of the anionic GP‐treated HCE cells. In vivo examination showed no serious irritation to the rabbit eyes. Furthermore, corneal thickness and ocular pressure in the eyes of the treated rabbits were similar to those in the eyes of normal rabbits. Microscopic examination of corneal cryosections showed widely distributed fluorescent nanocarriers, from the anterior to the posterior part of the cornea of the GP(+) group, and higher fluorescence intensity in the GP(+) group was also observed. In conclusion, GPs as cationic colloidal carriers were efficiently adsorbed on the negatively charged cornea without irritating the eyes of the rabbits and can be retained in the cornea for a longer time. Thus, GPs(+) have a great potential as vehicles for ocular drug delivery.
Within the heterogeneous tissue architecture, a comprehensive understanding of how cell shapes regulate cytoskeletal mechanics by adjusting focal adhesions (FAs) signals to correlate with the lineage commitment of mesenchymal stromal cells (MSCs) remains obscure. Here, via engineered extracellular matrices, we observed that the development of mature FAs, coupled with a symmetrical pattern of radial fiber bundles, appeared at the right-angle vertices in cells with square shape. While circular cells aligned the transverse fibers parallel to the cell edge, and moved them centripetally in a counter-clockwise direction, symmetrical bundles of radial fibers at the vertices of square cells disrupted the counter-clockwise swirling and bridged the transverse fibers to move centripetally. In square cells, the contractile force, generated by the myosin IIA-enriched transverse fibers, were concentrated and transmitted outwards along the symmetrical bundles of radial fibers, to the extracellular matrix through FAs, and thereby driving FA organization and maturation. The symmetrical radial fiber bundles concentrated the transverse fibers contractility inward to the linkage between the actin cytoskeleton and the nuclear envelope. The tauter cytoskeletal network adjusted the nuclear-actomyosin force balance to cause nuclear deformability and to increase nuclear translocation of the transcription co-activator YAP, which in turn modulated the switch in MSC commitment. Thus, FAs dynamically respond to geometric cues and remodel actin cytoskeletal network to re-distribute intracelluar tension towards the cell nucleus, and thereby controlling YAP mechanotransduction signaling in regulating MSC fate decision. STATEMENT OF SIGNIFICANCE: We decipher how cellular mechanics is self-organized depending on extracellular geometric features to correlate with mesenchymal stromal cell lineage commitment. In response to geometry constrains on cell morphology, symmetrical radial fiber bundles are assembled and clustered depending on the maturation state of focal adhesions and bridge with the transverse fibers, and thereby establishing the dynamic cytoskeletal network. Contractile force, generated by the myosin-IIA-enriched transverse fibers, is transmitted and dynamically drives the retrograde movement of the actin cytoskeletal network, which appropriately adjusts the nuclear-actomyosin force balance and deforms the cell nucleus for YAP mechano-transduction signaling in regulating mesenchymal stromal cell fate decision.
Calcium phosphate ceramics used in dentistry and orthopedics are some of the most valuable biomaterials, owing to their excellent osteoconduction, osteoinduction, and osseointegration. Osteoconduction and osteoinduction are critical targets for bone regeneration, and osseointegration is essential for any dental implantations. In this study, a hydroxyapatite (HAp) hybrid coating layer with the sequential release of bone morphogenetic protein 2 (BMP-2) was deposited onto an etched titanium substrate by electrochemical deposition. The resulting release of BMP-2 from Ti–HAp was assessed by immersing samples in a simulated buffer fluid solution. Through coculture, human osteosarcoma cell proliferation and alkaline phosphatase activity were assessed. The characteristics and effect on cell proliferation of the hybrid coatings were investigated for their functionality through X-ray diffraction (XRD) and cell proliferation assays. Findings revealed that −0.8 V vs. Ag/AgCl (3 M KCl) exhibited the optimal HAp properties and a successfully coated HAp layer. XRD confirmed the crystallinity of the deposited HAp on the titanium surface. Ti-0.8 V Ti–HAp co-coating BMP sample exhibited the highest cell proliferation efficiency and was more favorable for cell growth. A successful biocompatible hybrid coating with optimized redox voltage enhanced the osseointegration process. The findings suggest that this technique could have promising clinical applications to enhance the healing times and success rates of dental implantation.
Silicon nanowire field effect transistor (NWFET) sensors have been demonstrated to have high sensitivity, are label free, and offer specific detection. This study explored the effect of nanowire dimensions on sensors’ sensitivity. We used sidewall spacer etching to fabricate polycrystalline silicon NWFET sensors. This method does not require expensive nanoscale exposure systems and reduces fabrication costs. We designed transistor sensors with nanowires of various lengths and numbers. Hepatitis B surface antigen (HBsAg) was used as the sensing target to explore the relationships of nanowire length and number with biomolecule detection. The experimental results revealed that the sensor with a 3 µm nanowire exhibited high sensitivity in detecting low concentrations of HBsAg. However, the sensor reached saturation when the biomolecule concentration exceeded 800 fg/mL. Sensors with 1.6 and 5 µm nanowires exhibited favorable linear sensing ranges at concentrations from 800 ag/mL to 800 pg/mL. The results regarding the number of nanowires revealed that the use of few nanowires in transistor sensors increases sensitivity. The results demonstrate the effects of nanowire dimensions on the silicon NWFET biosensors.
1 February 2013 in Journal of Experimental & Clinical Medicine
A novel technique combination of ion bombardment (IB) and NH3 plasma treatment (PT) has been presented to yield a highly effective charge storage layer for Si/SiO2/Si3N4/SiO2/Si (SONOS)-type nonvolatile memory applications. The IB technique creates additional trap sites within the charge storage layer strikingly to enhance the charge trapping/detrapping efficiency of the storage layer, and the NH3 PT passivates shallow trap sites significantly to improve reliability characteristics. The distribution of trap sites corresponding with various energy levels is clearly described by discharge-based multipulse analysis. As compared with the control sample (without IB and NH3 PT), the ion-bombarded and NH3-plasma-passivated memory device has faster program/erase speeds and larger memory window. In addition, the competent reliability properties of the ion-bombarded and NH3-plasma-passivated memory, such as good endurance, long data retention, and acceptable disturbance, were also demonstrated in this letter.